Lancet Respiratory Medicine最新文献

{"title":"European Respiratory Society International Congress 2025","authors":"Priya Venkatesan","doi":"10.1016/s2213-2600(25)00366-2","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00366-2","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Early-life exposure to paracetamol versus ibuprofen</h2>Previous non-experimental studies suggest an association between paracetamol exposure in the first year of life and subsequent asthma and eczema developing in childhood; however, randomised trials are needed to establish whether a causal link truly exists. Stuart R Dalziel (University of Auckland, Auckland, New Zealand) presented 1-year results from the PIPPA Tamariki randomised <span><span>study</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> comparing the use of paracetamol versus ibuprofen in early life. The study included 3908 infants in New Zealand</section></section><section><section><h2>Astegolimab for COPD</h2>Triggers of exacerbations in chronic obstructive pulmonary disease (COPD) can release IL-33 that binds to the ST2 receptor and increase inflammation; therefore, targeting the IL-33/SL2 pathway is an area of therapeutic interest. Neil J Greening (University of Leicester, Leicester, UK) presented results from the phase 2b <span><span>ALIENTO trial</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> comparing astegolimab, a human IgG2 monoclonal antibody targeting ST2 and blocking IL-33 activity, versus placebo in current or former smokers aged 40–90 years</section></section><section><section><h2>Sotatercept for PAH</h2>Two studies were presented on sotatercept, a fusion protein that inhibits activin signalling, for the treatment of pulmonary arterial hypertension (PAH). In the first, Ioana R Preston (Tufts Medical Center, Boston, MA, USA) presented new safety data from the <span><span>SOTERIA</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> long-term follow-up study, the interim results for which were published <span><span>previously</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>. Chalmers commented “Sotatercept is a game changer in PAH supported by a series of impactful trials, [but] long-term safety of new therapies is</section></section><section><section><h2>Nerandomilast for IPF</h2>Justin M Oldham (University of Michigan, Ann Arbor, MI, USA) presented final data from the <span><span>FIBRONEER-IPF</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></pat","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"33 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Farming life: a double-edged sword for respiratory health.","authors":"The Lancet Respiratory Medicine","doi":"10.1016/S2213-2600(25)00331-5","DOIUrl":"10.1016/S2213-2600(25)00331-5","url":null,"abstract":"","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":" ","pages":"857"},"PeriodicalIF":32.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taladegib for the treatment of idiopathic pulmonary fibrosis (ENV-IPF-101): a multicentre, randomised, double-blind, placebo-controlled, phase 2a trial","authors":"T M Maher, J G Goldin, J Hood, J Pitman, M de los Rios, B P Hobbs, A B Yu-Lin, I Buendia-Roldan, F Thien, J W Song, P C Perea, A Ramírez-Rivera, A DiFrancesco","doi":"10.1016/s2213-2600(25)00239-5","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00239-5","url":null,"abstract":"<h3>Background</h3>The hedgehog (Hh) signalling pathway promotes fibrosis in idiopathic pulmonary fibrosis (IPF), an interstitial lung disease with a high mortality rate. Currently, there is no cure for IPF, and available anti-fibrotics only slow the rate of decline in lung function in IPF. We aimed to assess the safety and efficacy of taladegib (ENV-101), an Hh pathway inhibitor, in IPF in a phase 2a, proof-of-concept clinical trial.<h3>Methods</h3>ENV-IPF-101 was a randomised, double-blind, placebo-controlled, phase 2a trial conducted at 16 clinical sites in Australia, Canada, Malaysia, Mexico, and South Korea for patients with IPF older than 40 years who were not treated with concurrent IPF therapy. Patients were randomly assigned to taladegib 200 mg or placebo equivalent once daily, orally for 12 weeks, with a 6-week follow-up. The primary outcomes were safety in the intention-to-treat population and change from baseline in forced vital capacity (FVC) in the efficacy-evaluable population. Exploratory outcomes were measures of fibrosis on high-resolution CT (HRCT) in the efficacy-evaluable population. This study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT04968574</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>.<h3>Findings</h3>Between Aug 12, 2021, and July 28, 2023, 41 patients were randomly assigned to the taladegib group (n=21; three [14%] female and 18 [86%] male) or the placebo group (n=20; four [20%] female and 16 [80%] male). All treatment-emergent adverse events possibly or probably related to the study drug were grade 1 or 2, all except one were mild or moderate in severity, and none were serious adverse events. The most common treatment-emergent adverse events in the taladegib group were dysgeusia (12 [57%] of 21), muscle spasms (12 [57%] of 21), and alopecia (11 [52%] of 21); none of these events were reported in the placebo group, for which the most common adverse events reported were diarrhoea (four [20%] of 20), headache (three [15%] of 20), and dizziness (one [5%] of 20). Patients treated with taladegib had an improvement from baseline in FVC and across multiple HRCT-based measures of disease. Between-group differences in change from baseline to week 12 favoured taladegib for the efficacy measures of percent predicted FVC (3·95% [95% CI 0·31–7·60]; p=0·035; mean change from baseline of 1·9% in the taladegib group <em>vs</em> –1·3% for placebo), total lung capacity by HRCT (257·0 mL [95% CI 86·8–427·2]; p=0·0040; mean change from baseline of 206·67 mL in the taladegib group <em>vs</em> –55·58 mL in the placebo group), and percent quantita","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"40 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hedgehog signalling: on the way to curing idiopathic pulmonary fibrosis","authors":"Paolo Spagnolo, Yet H Khor","doi":"10.1016/s2213-2600(25)00284-x","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00284-x","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"5 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inclusion of small airway dysfunction in asthma assessment and management: a place for impulse oscillometry?","authors":"Anna-Carin Olin","doi":"10.1016/s2213-2600(25)00325-x","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00325-x","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"94 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reframing remission in severe asthma: a conceptual framework for distinguishing disease activity versus damage","authors":"Celeste Porsbjerg, Hitasha Rupani, John D Brannan, Shigeharu Ueki, Martijn C Nawijn, Jonas S Erjefält, Pascal Chanez, Gary P Anderson, Ian D Pavord","doi":"10.1016/s2213-2600(25)00299-1","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00299-1","url":null,"abstract":"Remission is emerging as a feasible treatment goal in moderate-to-severe asthma, driven by the success of biologic therapies in controlling inflammation and reducing exacerbations. Yet current definitions of remission—focused on symptom control, lung function, and corticosteroid reduction—lack precision, can only be ascertained retrospectively, and do not reflect the underlying mechanisms and pathology that drive disease progression. This gap limits the clinical applicability of these definitions and might obscure opportunities for early, disease-modifying intervention. In this Series paper, we propose a refined framework for understanding and reaching remission, centred on distinguishing modifiable disease activity from irreversible remodelling and comorbidity-related factors that contribute to disease burden. We introduce the concept of at-risk asthma as a crucial phase characterised by high disease activity and immune dysregulation, in which timely intervention might prevent irreversible airway and extrapulmonary damage and support long-term disease modification. We examine how symptoms, lung function impairment, and exacerbations can arise from distinct and overlapping mechanisms, underscoring the need for careful attribution in clinical assessment. We also outline four key pathophysiological domains—airway hyper-responsiveness, immune hyper-responsiveness, immune remodelling, and structural remodelling—and describe their temporal evolution and implications for treatment responsiveness. Finally, we present a domain-based strategy for assessment and intervention, linking targeted therapies to underlying mechanisms. This approach supports more personalised treatment decisions and redefines remission, not simply as the absence of symptoms, but as stabilisation of disease biology. As the field advances towards earlier intervention and more tailored application of biologics in at-risk asthma, such a framework could be essential to improve long-term outcomes and prevent overtreatment of irreversible disease.","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"37 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and environmental risk factors for asthma: towards prevention","authors":"Gerard H Koppelman, Maria Pino-Yanes, Erik Melén, Pippa Powell, Ken R Bracke, Juan C Celedón, Guy G Brusselle","doi":"10.1016/s2213-2600(25)00256-5","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00256-5","url":null,"abstract":"Asthma is a common chronic airway disease affecting an estimated 260 million individuals of all ages worldwide, contributing to substantial morbidity, mortality, and economic burden. Asthma is heterogeneous in age at onset (childhood <em>vs</em> adult onset), clinical presentation, type of underlying airway inflammation (type 2 high <em>vs</em> type 2 low), prognosis, and treatment response. Asthma is caused by multiple genetic and environmental factors, and possibly their interaction, across the life course. Genetic studies have provided important insights into the pathogenesis, biology, and immunology of asthma, fostering drug discovery. The role of polygenic risk scores in aiding asthma diagnostics and delineating individuals at high risk of asthma development is becoming more evident. Four modifiable environmental, social, and lifestyle risk factors for asthma are responsible for nearly 30% of the global disability-adjusted life-years asthma burden: high BMI, occupational exposures, NO₂ (as a proxy for traffic-related air pollution), and smoking. These modifiable risk factors offer substantial opportunities for primary prevention of asthma, at the individual and societal level. National, regional, and global strategies aligned with the UN Sustainable Development Goals are urgently needed to attenuate the predicted increase in asthma cases by 2050.","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"34 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guy Brusselle: using hypothesis-driven and hypothesis-free research to aid people with asthma","authors":"Peter Ranscombe","doi":"10.1016/s2213-2600(25)00337-6","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00337-6","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"116 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the role of small airway dysfunction in relation to exacerbation risk in patients with well controlled asthma (ATLANTIS): an observational study","authors":"Stanley P Galant, Pauline J M Kuks, Tessa M Kole, Monica Kraft, Salman Siddiqui, Leonardo M Fabbri, Bianca Beghé, Klaus F Rabe, Alberto Papi, Christopher E Brightling, Dave Singh, Janwillem W H Kocks, Laura Franzini, Judith M Vonk, Huib A M Kerstjens, Irene H Heijink, Simon D Pouwels, Dirk-Jan Slebos, Maarten van den Berge","doi":"10.1016/s2213-2600(25)00283-8","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00283-8","url":null,"abstract":"&lt;h3&gt;Background&lt;/h3&gt;Recent surveys suggest that asthma remains inadequately controlled in more than 50% of adults with asthma despite guideline-based standard therapy. Small airways are often under-recognised as major sites of airway obstruction and inflammation. This might be related to lack of assessment with current tools such as impulse oscillometry, and thus under-treatment might explain inadequate control. Small airway dysfunction, which is common in adults with well controlled asthma, might represent an important biomarker of future risk of exacerbations. We aimed to investigate whether small airway dysfunction is present in patients with well controlled asthma and, if so, whether it is a risk factor for future exacerbations in this population.&lt;h3&gt;Methods&lt;/h3&gt;The observational Assessment of Small Airways Involvement in Asthma (ATLANTIS) study included 773 extensively characterised patients with asthma aged 18–65 years from 29 primary and specialty clinics in nine countries from June 30, 2014, to March 3, 2017. Patients were required to be diagnosed with asthma at least 6 months before inclusion based on evidence of airway hyper-responsiveness, bronchodilator reversibility, or peak expiratory flow variability. Patients were required to have stable asthma, defined as no asthma exacerbations and regular asthma treatment at a consistent dose for 8 weeks before baseline visits. The current analysis included patients with well controlled asthma, defined as an Asthma Control Questionnaire (ACQ-6) score of less than 0·75 at baseline. Small airway dysfunction was defined, based on deviation from predicted values of impulse oscillometry parameters, as a Z score of more than 1·645 for R5–R20 (resistance at 5 Hz minus resistance at 20 Hz) and AX (area of reactance) and a Z score of less than –1·645 for X5 (reactance at 5 Hz), with additional analyses exploring severe small airway dysfunction (Z score of 3 or –3). ATLANTIS is registered with &lt;span&gt;&lt;span&gt;ClinicalTrials.gov&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;NCT02123667&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;.&lt;h3&gt;Findings&lt;/h3&gt;Of 773 patients, ACQ-6 assessments were available for 772 patients. Among these patients, 384 (50%) were classified as having well controlled asthma, and small airway dysfunction was present in 108 (36% [95% CI 30–41]) of 304 patients with impulse oscillometry data available for R5–R20, 89 (34% [28–42]) of 261 patients with data for AX, and 79 (26% [21–31]) of 303 patients with data for X5. In the multivariable analysis, we found that R5–R20-defined small airway dysfunction was associated with increased risk of future exacerbati","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"75 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking immunotherapy in patients with SCLC with poor performance status","authors":"Noemi Reguart, Lizza E L Hendriks","doi":"10.1016/s2213-2600(25)00290-5","DOIUrl":"https://doi.org/10.1016/s2213-2600(25)00290-5","url":null,"abstract":"No Abstract","PeriodicalId":51307,"journal":{"name":"Lancet Respiratory Medicine","volume":"1 1","pages":""},"PeriodicalIF":76.2,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}